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D J McCarty

Publications and source records attributed to D J McCarty.

At least 91 records · Page 5Linked to original sources
PubMed1989

Immune complex disease and gynecomastia.

A man with arthritis, gynecomastia and a rash histologically showing leukocytoclastic vasculitis, dermatitis herpetiformis and immunoglobulin G deposits at the dermoepidermal junction is reported. In contrast to cases of systemic lupus erythematosus (SLE) associated with vesiculobullous eruptions and similar histological features, our patient had neither bullae nor serological evidence of SLE. Conversely, no men already reported had evidence of feminization. Thus, our case appears to be unique.

Adult↗
PubMed1989

Aspirin and the treatment of rheumatoid arthritis.

The recent development of other nonsteroidal anti-inflammatory agents (NSAIDs) has challenged the role of aspirin in the initial treatment of rheumatoid arthritis. The ready availability of aspirin as "an over-the-counter" preparation has contributed to its low esteem among both patients and physicians as a truly potent anti-inflammatory agent. But whether these newer, more expensive NSAIDs are more efficacious in the treatment of rheumatoid arthritis than aspirin remains to be proven. Most clinical trials of the newer agents have compared their efficacy against fixed doses of aspirin which were almost always too small to produce optimal anti-inflammatory serum salicylate levels. In our experience, individually tailored doses of aspirin remains the most predictable and consistently effective NSAID available for the initial treatment of rheumatoid arthritis. We also want to make it clear that we almost never rely on aspirin or other NSAIDs to control seropositive rheumatoid arthritis. Their chief advantage is rapidity of action. We do rely on the use of remittive agents to control rheumatoid joint inflammation, in conjunction with aspirin or other NSAID.

Animals↗
PubMed1988

Arthritis associated with calcium oxalate crystals in an anephric patient treated with peritoneal dialysis.

We report a case of calcium oxalate arthropathy in a woman undergoing intermittent peritoneal dialysis who was not receiving pharmacologic doses of ascorbic acid. She developed acute arthritis, with calcium oxalate crystals in Heberden's and Bouchard's nodes, a phenomenon previously described in gout. Intermittent peritoneal dialysis may be less efficient than hemodialysis in clearing oxalate, and physicians should now consider calcium oxalate-associated arthritis in patients undergoing peritoneal dialysis who are not receiving large doses of ascorbic acid.

Aged↗
PubMed1988

Synovial fluid inorganic pyrophosphate concentration and nucleotide pyrophosphohydrolase activity in basic calcium phosphate deposition arthropathy and Milwaukee shoulder syndrome.

Synovial fluid (SF) inorganic pyrophosphate (PPi) concentration is elevated in calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy. Since CPPD and basic calcium phosphate (BCP) crystals often are present in the same joints, we determined [PPi] and activity of the PPi-generating enzyme, nucleotide pyrophosphohydrolase (NPPH), in SF from the joints of patients with various arthropathies, including those with BCP crystals. We found elevated SF [PPi] in joints with BCP crystals, as well as in joints with CPPD crystals. The presence of BCP crystals in synovial fluids was also predictive of elevated NPPH activity.

Calcium Phosphates↗
PubMed1988

Crystal identification in human synovial fluids. Methods and interpretation.

Gout is largely solved, both from diagnostic and therapeutic standpoints. Acute gout is easily suppressed and joint destruction can be prevented and at least reversed by lowering the serum uric acid level with relatively safe and very effective drugs. But the arthritides associated with the calcium-containing crystals remain untreatable by other than symptomatic or surgical means. If we had a method or a drug to remove CPPD or BCP crystal deposits from joints, would it make any difference in the severity of the arthritis? Which of the paradigms shown in Figure 5 holds for these crystals? If joint damage directly follows crystal deposition as in gout, then crystal removal should prove prophylactic. The unusual pattern of joint degeneration associated with polyarticular CPPD crystal deposition and the initial appearance of CPPD crystals in radiographically normal cartilage favors this idea. But radiologic chondrocalcinosis appearing in knees subjected years before to meniscectomy but not in the contralateral knees suggests that crystal deposition, in these cases at least, is secondary to trauma or surgery. If degeneration of cartilage precedes crystal deposition, as it probably does in the case of BCP crystals, then crystal removal may not be particularly helpful. Dieppe and his colleagues proposed that the calcium crystals provide a positive feedback (amplification) loop. This represents the minimalistic view of their importance. The biologic consequences of the calcium crystal deposition diseases are now being explored at the molecular level. Much more data are needed before more than speculative answers to the questions posed here can be formulated. Calcium crystal deposition is more common in older persons. The degenerative and destructive arthropathies associated with them will predictably become increasingly common as our population ages.

Arthritis↗
PubMed1988

Mechanisms of connective tissue damage by crystals containing calcium.

From available clinical, radiographic, and synovial fluid findings, coupled with in vivo radiolabelled crystal turnover data and in vitro experimental data, a hypothesis has been formulated relative to the pathogenesis of BCP crystal deposition diseases (Fig. 2). Synovial lining cells phagocytose BCP crystals and particulate collagens in the joint fluid. During and/or after internalization these cells are stimulated in a variety of ways: 1) protease synthesis and secretion is relentlessly stimulated, which may damage joint tissues producing clinically evident loss of collagenous tissues including cartilage, bone, and tendon, and which may release additional amounts of crystals and particulate collagens into the synovial fluid, completing a vicious cycle; 2) PGE2 production is greatly augmented; 3) DNA synthesis is stimulated as a result of increased inositol phospholipid turnover and intracellular crystal dissolution. The increased number of synovial cells also augments the total local generation of proteases and prostenoids. Mechanical factors such as trauma or joint overuse also contribute to the pathogenesis of joint destruction as discussed in the article on the clinical aspects of BCP crystal deposition.

Animals↗
PubMed1988

Clinical aspects of basic calcium phosphate crystal deposition.

Our present understanding of the mechanisms of pathologic calcification is quite limited. Therefore, no reliable method exists to prevent calcium crystal deposition. Low doses of warfarin have been employed in some cases of soft tissue calcification because it depresses the synthesis of the vitamin K-dependent GLA protein (gamma carboxyglutamic acid), which has been implicated in the process of calcification. Reports of success must be tempered by the lack of a controlled study. Probenecid has also been utilized in the treatment of calcinosis.

Arthritis↗
PubMed1988

Periarthritis associated with basic calcium phosphate crystal deposition and low levels of serum alkaline phosphatase--report of three cases from one family.

Three siblings, 2 women and one man, from an Iranian-Jewish family with low serum levels of alkaline phosphatase (liver fraction) and symptomatic calcific periarthritis of multiple joints are described. Both parents and 2 additional siblings had normal serum alkaline phosphatase levels and no joint symptoms. The disease in the proposita, a 49-year-old woman, showed 3 unusual features: (1) no rise in acute phase serum proteins despite severe attacks of periarthritis; (2) refractoriness to treatment; (3) pure octacalcium phosphate found in a deposit obtained by biopsy.

Adult↗
PubMed1987

Endocytosis is required for the mitogenic effect of basic calcium phosphate crystals in fibroblasts.

Basic calcium phosphate (BCP) crystals stimulate mitosis of cultured fibroblasts and synoviocytes in vitro. Although intimate crystal-cell contact is required for mitogenesis, and lysosomotropic agents such as chloroquine and ammonium chloride block the mitogenic effect of crystals, the requirement of endocytosis has not been demonstrated. Synthetic BCP crystals, uniformly trace-labeled with 45Ca, were added to cultured, quiescent, confluent human foreskin fibroblasts in the presence or absence of ammonium chloride. After 4 or 24 hours, cultures were pulsed with 3H thymidine. The cells were then released with EDTA and trypsin, and fractionated on preformed Percoll density gradients. Fractions were analyzed for incorporation of 45Ca and [3H]thymidine and cell number. The cells containing 45Ca crystals also were heavily labeled with thymidine. Ammonium chloride decreased the amount of crystals endocytosed, and inhibited mitogenesis. These data suggest that mitogenesis induced by BCP crystals is preceded by endocytosis and dissolution in the acidic environment of phagolysosomes.

Calcium Phosphates↗
PubMed1987

Suppression of active collagenase from calcified lapine synovium by Arteparon.

Collagenase has been implicated in the pathogenesis of several arthropathies. Arteparon [glycos-aminoglycan (GAG) polysulfate] is a proteinase inhibitor that is being investigated as a therapeutic agent in osteoarthritis. We found that cultures of calcified lapine synovium release collagenase, one tenth of which is already activated. Normal synovium produces no active collagenase. GAG polysulfate suppresses the amount of active collagenase by one half. GAG polysulfate may interfere with the activation process of collagenase.

Animals↗
PubMed1987

Osteonecrosis, fractures, and protrusio acetabuli secondary to x-irradiation therapy for prostatic carcinoma.

Two years after pelvic irradiation for prostatic cancer, bilateral protrusio acetabuli and collapse of the right femoral head requiring prosthetic arthroplasty developed in a 73-year-old man with chronic rheumatoid arthritis. There was no evidence of metastases. Histologic evaluation showed empty lacunae in the bone but no evidence of obliterative endarteritis. Osteonecrosis and pathologic fractures constitute a rare complication of high voltage irradiation.

Acetabulum↗
PubMed1986

Arthropathies associated with calcium-containing crystals.

Monosodium urate crystals are clearly related to acute attacks of gout and to the hard tissue destruction of chronic tophaceous gout. Fortunately, the acute attacks are readily treated with anti-inflammatory drugs, and destructive changes due to tophi may be prevented or reversed, at least in part, by the intelligent control of serum urate levels. Control of gout is one of the premier success stories of modern medicine. In contrast, the number of patients who have arthritis associated with crystals that contain calcium appears to be rising--perhaps a function of better recognition, perhaps related to the aging of the population. CPPD and BCP crystals can be associated with acute or subacute inflammation, but as in acute gout, it is easily controlled with anti-inflammatory drugs or by local injections of corticosteroids. A direct relationship of BCP and CPPD crystals to the associated destructive arthropathies has been hypothesized and is supported by clinical observations, animal studies, and in vivo experiments. Unlike gout, which is usually associated with a systemic metabolic abnormality (i.e., hyperuricemia), calcium crystals deposition seem to be a localized phenomenon, although numerous local sites in several joints are often involved in a given patient. Tissue degeneration in gout clearly follows (tophaceous) crystal deposition. Calcium crystal deposition may follow, rather than precede, destructive joint changes. Alternatively, both destructive changes and crystal deposition may derive independently from a common, still obscure, biochemical abnormality of joint tissues. P. A. Dieppe and colleagues believe that calcium crystal deposition follows either primary or secondary tissue degeneration but that the crystals exert a positive feedback effect (amplification loop) that accelerates degeneration. Each of those formulations of a pathogenetic role for crystals may be true in a given case, analogous to the etiology of primary and secondary forms of hyperuricemia and to sodium urate crystal deposition coexistent with osteoarthritis (tophus formation in Heberden's nodes). Conclusive proof of a significant role for BCP or CPPD crystals in the pathogenesis of human joint tissue damage depends on interrupting the postulated disease mechanism and showing that this prevents joint deterioration and leads to significant repair of existing damage. Our current position is somewhat analogous to that of our colleagues who had to contend with management of gouty arthritis before the advent of effective drugs for control of hyperuricemia.

Aged↗
PubMed1986

Treatment of intractable rheumatoid arthritis with combined cyclophosphamide, azathioprine, and hydroxychloroquine. A follow-up study.

Cyclophosphamide, azathioprine, and hydroxychloroquine sulfate were prescribed for 31 patients (26 women and five men) with rheumatoid arthritis refractory to conventional therapy. Maintenance drug dosages (mean +/- SD) were as follows: cyclophosphamide, 30 +/- 24 mg/day; azathioprine, 74 +/- 44 mg/day; and hydroxychloroquine sulfate, 210 +/- 92 mg/day. Disease suppression began in 30 patients within three to 24 months (mean, nine months). Results after 43 months (range, 12 to 102 months) were as follows: 16, complete remission; seven, near remission; seven, partial disease suppression; one, no response. None remained in prolonged remission without some form of therapy. Treatment was discontinued in three patients because of pulmonary infection (two) or thrombocytopenia (one). Four patients had five malignant neoplasms (surgical cures) before therapy (two breast, one colon, one melanoma, one endometrial); four patients developed a malignant neoplasm during combined drug therapy (one colon, one endometrial, one lung, one erythroleukemia); and three died. The absolute risk of malignancy from combined drug therapy is still unclear. We concluded that combined use of remittive agents may have promise in treatment of severe rheumatoid arthritis; cyclophosphamide should be replaced with a nonalkylating agent; and the place of combined drug therapy remains uncertain in the absence of controlled trials.

Adult↗